Dataset Information

ALK Rearrangement-Positive Pancreatic Cancer with Brain Metastasis Has Remarkable Response to ALK Inhibitors: A Case Report.

ABSTRACT: Patients with metastatic pancreatic cancer typically have poor prognosis due to the limited effectiveness of existing treatment options. ALK rearrangement-positive is rare in pancreatic cancer, but may occur in those with KRAS-wild type. We present a 34-year-old young man with ALK rearrangement-positive and KRAS-wild pancreatic cancer who had a remarkable response to crizotinib after resistance to prior chemotherapy and re-response to alectinib after brain metastases developed. This clinical observation suggests that comprehensive molecular profiling to guide targeted therapies is not only feasible, but also significantly improves survival outcomes for a subgroup of patients with pancreatic cancer.

SUBMITTER: Ou K

PROVIDER: S-EPMC8456297 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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ALK Rearrangement-Positive Pancreatic Cancer with Brain Metastasis Has Remarkable Response to ALK Inhibitors: A Case Report.

Ou Kai K Liu Xiu X Li Weihua W Yang Yi Y Ying Jianming J Yang Lin L

Frontiers in oncology 20210906

Patients with metastatic pancreatic cancer typically have poor prognosis due to the limited effectiveness of existing treatment options. ALK rearrangement-positive is rare in pancreatic cancer, but may occur in those with KRAS-wild type. We present a 34-year-old young man with ALK rearrangement-positive and KRAS-wild pancreatic cancer who had a remarkable response to crizotinib after resistance to prior chemotherapy and re-response to alectinib after brain metastases developed. This clinical obs ...[more]

PMID: 34568053

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Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic carcinomas. Prognosis is poor with a worldwide five-year survival rate of 2-9%. Extent of metastasis is a prognostic factor. Most common metastatic sites include the liver, peritoneum, lung, and bones. We report a case of distant metastasis of PDAC to the left choroid.Case descriptionThis patient is a 59-year-old Caucasian male who initially presented with right flank pain progressing to exercise and activity impairment. Abdominal computed tomography scan showed a pancreatic tail mass subsequently confirmed as PDAC via endoscopic ultrasound with fine needle aspiration. Prior to treatment initiation, patient was referred to ophthalmology for acute vision changes. Evaluation revealed left eye pigmentary changes overlying subretinal fluid (SRF) along with peripheral retinal depigmentation indicative of choroidal metastasis. As of this report submission, patient has completed his initial 6-month course of gemcitabine/paclitaxel protein-bound/cisplatin with partial response. He remains active on his second line of chemotherapy. Visual disturbances and evidence of choroidal metastasis continue to resolve.ConclusionsPDAC is often identified at a late stage, with metastasis or local advancement identified in 80-85% of first diagnoses. This is thought to account for its poor median survival of two to eleven months. The retinal choroid is an extremely rare site of PDAC metastasis, with less than ten cases reported in literature. In this patient, the choroid was the first confirmed metastatic site and represented distant metastasis. Nevertheless, this patient continues to do well and is expected to exceed the upper bound median survival of 11 months following systemic chemotherapy. From this case, we note that distant metastasis prior to treatment initiation may not predict worse prognosis. Systemic chemotherapy was effective in both primary tumor shrinkage as well as regression of choroidal metastasis, leading to improvement in visual symptoms. This suggests that while choroidal metastasis should not be missed in patients with PDAC, systemic chemotherapy may be effective in mitigating collateral symptomatology and thus preserving quality of life.

Project description:Background: ALK inhibitors have shown positive advance in the treatment of ALK+ NSCLC. They have achieved better results in prolonging the progression free survival and improving quality of life in comparison to chemotherapy. We have assembled the evidence related to the efficacy and safety of these agents in the treatment of ALK positive NSCLC. Materials and Methods: A comprehensive search was conducted using electronic databases of PubMed, Medline and Cochrane Library to identify the studies involving comparison of ALK inhibitors to chemotherapy and Next generation ALK inhibitors to crizotinib. PFS was the primary outcome while other outcomes like ORR, adverse events, quality of life and OS were also analyzed and compared. Hazard ratios and odds ratios obtained were analyzed using fixed effect or random effects model in Review Manager Software. Results: A total of 12 studies (n = 3,297) met the criteria for inclusion in this review and meta-analysis. ALK inhibitors including crizotinib, ceritinib and alectinib revealed significantly better PFS (HR 0.42 [0.35, 0.50; p < 0.00001]), ORR (Overall OR 6.59 [4.86, 8.94; p < 0.00001] as compared to chemotherapy in the first line as well as second line treatment settings. Intracranial response rate was better with ALK inhibitors (ceritinib and alectinib) as compared to chemotherapy OR 6.51 [2.86, 14.83; p < 0.00001]. No significant increase in grade 3 or 4 adverse events was observed with crizotinib (OR 1.21 [0.82, 1.77; p = 0.34]) or ceritinib (OR 1.49 [0.86, 2.57; p = 0.17]) when compared to chemotherapy individually. Quality of life indicators assessed were significantly improved with ALK inhibitors. Next generation agents (ceritinib, alectinib and brigatinib) revealed significant improvement in PFS (HR 0.50 [0.43, 0.57; p < 0.00001]), ORR (OR 1.57 [1.21, 2.04; p = 0.0006]) in comparison to crizotinib. Next generation agents (Alectinib and brigatinib) yielded better response intra-cranially than crizotinib in terms of objective response rate (OR 5.87 [3.49, 9.87; p < 0.00001]) and time to CNS progression (HR 0.25 [0.13, 0.46; p < 0.0001]). Alectinib by far resulted in fewer adverse events than chemotherapy or crizotinib. Conclusions: Overall ALK inhibitors are safe and effective treatment option in ALK+ non-small cell lung cancer. Of the ALK inhibitors, Next generation agents in particular alectinib and brigatinib are safer and more effective intra-cranially and can be preferred as first option.

Dataset Information

ALK Rearrangement-Positive Pancreatic Cancer with Brain Metastasis Has Remarkable Response to ALK Inhibitors: A Case Report.

Publications

ALK Rearrangement-Positive Pancreatic Cancer with Brain Metastasis Has Remarkable Response to ALK Inhibitors: A Case Report.

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